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预后生物标志物复制因子 C 亚基 5 及其与急性髓系白血病免疫浸润的相关性。

Prognostic biomarker replication factor C subunit 5 and its correlation with immune infiltrates in acute myeloid leukemia.

机构信息

Department of Pediatric Surgery, Wenzhou Medical University, Wenzhou, People's Republic of China.

Department of Pediatric Surgery, Lishui people's Hospital, Lishui, People's Republic of China.

出版信息

Hematology. 2022 Dec;27(1):555-564. doi: 10.1080/16078454.2022.2072064.

Abstract

OBJECTIVE

To determine the role of replication factor C subunit 5 (RFC5) in acute myeloid leukemia (AML) from four aspects: expression, prognosis, biological functions, and its effects on the immune system.

METHODS

The RFC5 gene expression and survival analyses, biological function analyses including functional enrichment analysis of genes co-expressed with RFC5, RFC5-interacted gene network construction, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed using data based on GDC TCGA and GEO. The CIBERSORT algorithm was employed to quantify immune cell fractions. All the statistical analyses were performed in SPSS software, GraphPad Prism, and R software.

RESULTS

RFC5 expression was abnormally expressed in AML ( <0.05). Notably, differential RFC5 expression was observed among different FAB AML subtypes and hematopoietic lineages (all <0.05). More importantly, high RFC5 expression served as an independent prognostic factor for the poor overall survival of AML patients ( <0.001). Enrichment analyses revealed that RFC5 was involved in cell cycle-related pathways in AML. CIBERSORT analysis showed high proportions of M2 macrophages in the high RFC5 expression group.

CONCLUSIONS

RFC5 might serve as an effective and robust biomarker for the diagnosis and prognosis of AML. RFC5 might be involved in the AML progression via cell cycle regulation. Moreover, the correlation between RFC5 and immune cells might provide potential assistance for AML treatment.

摘要

目的

从表达、预后、生物学功能和对免疫系统的影响四个方面来确定复制因子 C 亚基 5(RFC5)在急性髓系白血病(AML)中的作用。

方法

利用 GDC TCGA 和 GEO 数据库中的数据,进行 RFC5 基因表达和生存分析、与 RFC5 共表达基因的功能富集分析、RFC5 相互作用基因网络构建、基因集富集分析(GSEA)和免疫浸润分析,采用 SPSS 软件、GraphPad Prism 和 R 软件进行所有统计分析。采用 CIBERSORT 算法量化免疫细胞分数。

结果

AML 中 RFC5 表达异常(<0.05)。值得注意的是,不同 FAB AML 亚型和造血谱系之间存在差异的 RFC5 表达(均<0.05)。更重要的是,高 RFC5 表达是 AML 患者总生存期不良的独立预后因素(<0.001)。富集分析显示,RFC5 参与 AML 中细胞周期相关途径。CIBERSORT 分析显示高 RFC5 表达组中 M2 巨噬细胞比例较高。

结论

RFC5 可能是 AML 诊断和预后的有效且稳健的生物标志物。RFC5 可能通过细胞周期调控参与 AML 的进展。此外,RFC5 与免疫细胞之间的相关性可能为 AML 治疗提供潜在帮助。

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